Cancer gene therapy – state-of-the-art

A number of gene therapy clinical trials are being carried out the world over. Gene therapy is being applied in (I) cancer diseases, involving the largest number of patients, (II) monogenic diseases, (III) infectious diseases, (IV) vascular diseases, (V) autoimmune diseases and others. In the last decade, several strategies of cancer gene therapy have emerged due to a rapid development of gene delivery systems, both viral (recombinant retroviruses, adenoviruses, AAVs, herpes viruses) and nonviral (liposomes, gene guns, electroporation). To date four main strategies of cancer gene therapy have been evaluated in clinical trials: (I) immunogene therapy, (II) suicide gene therapy, (III) antiangiogenic gene therapy, (IV) and administration of tumour suppressor genes.These strategies mostly involve: malignant melanoma, prostate cancer, renal cell cancer, colon cancer, breast and ovarian cancers, lung cancers, neoplastic diseases of the blood and brain tumours.At the Department of Cancer Immunology at the GreatPoland Cancer Center Gene Modified Tumour Vaccine has been tested in malignant melanoma patients for more than six years. Due to encouraging results from phase I and II of clinical trials a phase III was designed and will be started in 2003.     

Cancer Res:肿瘤形成新机制

正在一项新的研究中,来自美国罗格斯大学和哥伦比亚大学的研究人员鉴定出一个基因在肺部结节性硬化症的肿瘤形成中起着关键性的作用。这一发现可能为人们提供一种潜在的新药物靶标,也可能改变人们对肿瘤形成的常规认识。结节性硬化症(tuberous sclerosis complex,TSC)是一种罕见的疾病,在这种疾病中,良性肿瘤在包括肺部、大脑、肾脏、眼睛和心脏在内的重要     

Cancer Cell:癌症治疗新思路

<正>近年来,热门的癌症化个体化治疗方案往往聚焦于,与不同类型的癌症相关联的,特异性的基因突变。不同于以往的癌症作用靶点,近日,来自Saint Louis大学的研究人员们首次发现,一种靶向Warburg效应的药物,可以从根源上阻断癌症的能量来源,从而使癌症细胞停止生长。这项研究结果最近发表于Cancer Cell杂志上。我们知道,所有的生物均有利用能量的能力,即代谢。癌症细胞大大地加快了代谢过程,使突变的细胞疯狂地生长。早在20世纪初,科学家们     

Does Cancer Solve an Optimization Problem?

Many cancers are characterized by a high degree of aneuploidy, which isbelieved to be a result of chromosomal instability (CIN). The precise role of CIN incancer is still the matter of a heated debate. We present a quantitative framework forexamining the selection pressures acting on populations of cells and weigh the \pluses"and \minuses" of CIN from the point of view of a sel¯sh cell. We calculate the optimalrate of chromosome loss assuming that cancer is initiated by inactivation of a tumorsuppressor gene followed by a clonal expansion. The resulting rate, p* ~ ¼ 10^-2 per celldivision per chromosome, is similar to that obtained experimentally by Lengauer et al(1997). Our analysis further suggests that CIN does not arise simply because it allowsa faster accumulation of carcinogenic mutations. Instead, CIN must arise because ofalternative reasons, such as environmental factors, epigenetic events, or as a directconsequence of a tumor suppressor gene inactivation. The increased variability aloneis not a su±cient explanation for the presence of CIN in the majority of cancers.     

Cancer: Bad luck or punishment?

Contrasting opinions on the role of extrinsic and intrinsic factors in cancer etiology (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81; Wu, S., et al. (2016) Nature, 529, 43-47) variously define priorities in the war on cancer. The correlation between the lifetime risk of several types of cancer and the total number of divisions of normal selfrenewing cells revealed by the authors has given them grounds to put forward the “bad luck” hypothesis. It assumes that ~70% of cancer variability is attributed to random errors arising during DNA replication in normal, noncancerous stem cells, i.e. to internal factors, which is impossible either to expect or to prevent. This assumption caused many critical responses that emphasize, on the contrary, the defining role of extrinsic factors in cancer etiology. The analysis of epidemio-logical and genetic data presented in this work testifies in favor of the “bad luck” hypothesis.     

Cancer immunotherapy: simply cell biology?

There is a clear need for improved cancer therapy and survival rates. Effective immunotherapy would be the treatment modality of choice from several viewpoints, and dendritic cell (DC)-based immunotherapy is emerging as the most promising approach to cancer immunotherapy. However, the plethora of approaches to DC-based cancer therapy now threatens to impede the development of an effective immunotherapy regime, as competing egos and commercial interests masquerade as scientific rigour. Here, I argue that the current controversies regarding the numerous approaches reflect the paucity of our immunological understanding, and present a simple cell biological analysis that defines the rationale for the development of effective cancer immunotherapy.